mibolerone and Ovarian-Neoplasms

The pathogenesis of epithelial ovarian cancer remains unclear. From epidemiological studies raised levels of androgens have been implicated to increase the risk of developing the disease. The purpose of this study was to determine the responses of normal human ovarian surface epithelium to androgens. We have established primary cultures of human ovarian surface epithelium from patients undergoing oophorectomy for benign disease. Total RNA was isolated from these cultures and expression of mRNA encoding for the androgen receptor was demonstrated using reverse transcriptase polymerase chain reaction. The presence of androgen receptor in sections of normal ovary was also investigated using an antibody against androgen receptor. The effects of androgens on DNA synthesis and cell death were determined. Eight out of eight (100%) cultures expressed mRNA encoding the androgen receptor. The presence of androgen receptor in ovarian surface epithelium of sections of normal ovaries was demonstrated in all sections. Mibolerone, a synthetic androgen, caused a significant stimulation of DNA synthesis in 5 out of 9 (55%) cultures when used at a concentration of 1 nM. Mibolerone also caused a significant decrease in cell death in 2 out of 5 (40%) cultures tested. We have demonstrated that the ovarian surface epithelium is an androgen responsive tissue and that androgens can cause an increase in proliferation and a decrease in cell death. These findings have important implications for the pathophysiology of ovarian carcinogenesis.

Topics: Androgens; Cell Death; Cell Division; Culture Techniques; Epithelium; Female; Humans; Nandrolone; Ovarian Neoplasms; Ovary; Receptors, Androgen

A study to determine the efficacy and safety of mibolerone following prolonged oral administration in the female dog was terminated after 9.6 yr. Histopathologic examination revealed the presence of small dense tumors in the ovaries of 12 of 92 dogs given mibolerone at the approximate efficacious dose. No such tumors were found in 60 vehicle control animals or 55 animals given exaggerated doses of mibolerone. The tumors were composed of dense fibrous connective tissue and incorporated occasional ovarian medullary tubules. The tumors appeared to grow by expansion with no evidence of invasion or metastasis and were diagnosed as fibromas.

Topics: Animals; Dog Diseases; Dogs; Estrus; Female; Fibroma; Leiomyoma; Nandrolone; Ovarian Neoplasms; Species Specificity